Ten-year improvement of insulin resistance and growth with recombinant human insulin-like growth factor 1 in a patient with insulin receptor mutations resulting in leprechaunism.

AIM: Leprechaunism, a rare genetic disease resulting from mutations in two alleles of the insulin receptor gene, is characterized by severe insulin resistance, retarded growth and, usually, premature death. The ability of treatment with recombinant human insulin-like growth factor 1 (rhIGF1) to improve metabolic and clinical parameters in the long-term is still controversial. METHODS: Mutations were looked for in the insulin receptor gene of a four-month-old female baby with leprechaunism. The patient's skin fibroblasts were analyzed for response to insulin and IGF1. At the clinical level, the very long-term effects of treatment with rhIGF1/rhIGFBP3 were evaluated by clinical and metabolic parameters. RESULTS: The patient's diagnosis was based on compound heterozygous mutations in two alleles of the insulin receptor gene, thus confirming leprechaunism. Cultured fibroblasts showed a decreased number of insulin receptors and were insulin-resistant. However, IGF1 was able to stimulate IGF1 receptor signalling, suggesting possible activation of a salvage pathway. Treatment with IGF1/IGFBP3 for 8.7 years, then IGF1 for 2 years, resulted in normalization of circulating levels of IGF1 and IGFBP3. Large daily variations in glycaemia and insulinaemia persisted, but mean glycaemia decreased. Regarding growth, the patient's BMI Z score normalized and length/height score improved. Our patient presented normal neurological development and academic achievement. The treatment was free of adverse effects. CONCLUSION: Our results provide evidence that rhIGF1 with and without rhIGFBP3 can prevent fatal outcomes, and improve growth and metabolic parameters, for more than 10 years in a patient with leprechaunism. Long-term rhIGF1 for severe insulin resistance syndrome should be considered.

[Natural history of vascular ports for hemodialysis after renal transplantation]. / Histoire naturelle des abords vasculaires pour l'hémodialyse après transplantation rénale.

INTRODUCTION: The objective of this study was to assess the long-term outcome of AV shunts in renal transplant recipients, to discuss mechanisms affecting their functioning and the surgical strategy designed to optimally preserve the venous capital in the hypothesis of a return to dialysis. MATERIALS AND METHODS: 160 renal transplant recipients, with a mean age of 47 years, were reviewed. AV shunts were performed at the wrist in 95% of cases and in the cubital fossa in 13% of cases. The AV shunt had been performed an average of 29 months before renal transplantation. RESULTS: 62% of AV shunts were considered to be functional with a mean follow-up of 69 months after transplantation and 95 months after creation. The intraoperative and early and late postoperative thrombosis rates were 6%, 7.5% and 17%, respectively. The AV shunt was subsequently closed in 12 patients (7.5%). CONCLUSION: Native distal AV shunts, although not used after renal transplantation, have a prolonged survival. The main risk is thrombosis which can be prevented intraoperative and perioperatively. These results encourage a conservative attitude to all well tolerated AV shunts.

[Glomerular nephropathy with IgA mesangium deposits and Crohn disease]. / Néphropathie glomérulaire à dépôts mésangiaux d'IgA et maladie de Crohn.

BACKGROUND: Renal disease is an unfrequent extraintestinal manifestation of chronic inflammatory bowel disease. CASE REPORT: A 12-year-old girl suffered from recurrent abdominal pain, diarrhea and growth impairment due to Crohn's disease of ileocaecal region. After six months of nutritional rehabilitation, an ileo-caecal resection was performed because of intestinal stenosis. The surgical procedure was followed by parietal abcess and cutaneous fistula. One year later, a purulent secretion came out of the fistula associated with fever, hematuria and acute renal failure. Renal biopsy confirmed IgA nephropathy. The course was favorable under parenteral nutrition and after surgical closure of the sigmoido-cutaneous fistula. The microscopic hematuria only persisted but the nephropathy did not relapse even during a further digestive exacerbation. CONCLUSION: IgA nephropathy has been reported in association with chronic inflammatory bowel disease. Its mechanism remains unclear: increased mucosal IgA production in inflammatory bowel, increased serum IgA and/or immune complex deposition in the renal mesangium appear the most relevant hypotheses.

[Neurotoxicity of acyclovir in peritoneal dialysis apropos of 1 case]. / Neurotoxicité de l'aciclovir chez le dialysé péritonéal à propos d'un cas.

We report a case of reversible myoclonic encephalopathy which appeared after intravenous acyclovir treatment in a patient in CAPD for which pharmacological dosages have been made in serum, peritoneal dialysate and cerebrospinal fluid (CSF). Encephalopathy appeared after two intravenous doses of 7.33 mg/kg (doses higher than recommended), administered on admission and 16 hours later. Pharmacological dosages indicated that acyclovir peritoneal clearance was negligible, and that acyclovir persisted a long time in plasma and CSF. Neurological symptoms persisted although serum concentrations returned to normal value. The diagnostic value of pharmacological dosages in serum and CSF is discussed. In addition, neurological symptoms disappeared following two consecutive hemodialysis procedures. Hence we suggest that hemodialysis could be used for drug removal in case of acyclovir overdose in CAPD patients.

[Prognosis and treatment of glomerulonephritis of periarteritis nodosa. The role of plasma exchange]. / Pronostic et traitement des glomérulonéphrites de la périartérite noueuse. Place des échanges plasmatiques.

Fourteen patients with polyarteritis nodosa complicated by histologically confirmed glomerulopathies were included in a prospective multi-center study comparing corticotherapy (group 1, n = 8) with combined cyclophosphamide and steroids (group 2, n = 6). Plasma exchanges were associated on a routine basis. The two groups were comparable apart from initially more severe renal impairment in group 1 (p less than 0.05). Initial control of the disease was obtained in 11 patients (7 from group 1, 4 from group 2) including the patients with oligoanuria. Six patients recovered, 3 had recurrence requiring chronic hemodialysis and 5 patients died from group 1 (p less than 0.05). These preliminary findings suggest that plasma exchange can contribute to control of polyarteritis nodosa with renal complications.

Fractional clearance of bromosulfonephthalein and metabolic clearance of antipyrine. Correlative study in liver diseases.

Antipyrine metabolic clearance and BSP fractional (K1) clearance relationship in liver disease is the object of this study. 47 patients have been examined (liver cirrhosis: 17, liver disease without cirrhosis: 15, patients with no liver disease: 15). Results are as follows: antipyrine metabolic clearance is significantly lower in patients with cirrhosis; BSP fractional clearance is significantly lower in liver disease with and without cirrhosis; the clearances are significantly linked in liver cirrhosis patients, but not in the other patient groups. The role of liver cell deficiency and blood flow decrease is discussed with result interpretation.